16 December 2009. Dublin-based Elan has seen its share of disappointment in recent immunotherapy trials for Alzheimer disease (see ARF related news story). Now it appears that their small molecule drug candidate ELND005 has run into some trouble. According to the company website, serious adverse events, including a high number of deaths, have prompted the company to drop the highest two doses (1,000 mg and 2,000 mg twice a day) of the compound in its ongoing Phase 2 trial (ELND005-AD201) and also reduce dosage in its open-label extension study (ELND005-AD251) to 250 mg twice a day.
ELND005 (previously known as AZD-103) is an inositol compound that can prevent formation of amyloid-β oligomers, which many scientists consider the most toxic form of the peptide. The compound reduces brain Aβ deposits in mouse models of AD and also protects the animals against cognitive decline (see ARF related news story). It also improves synaptic function in neurons treated with Aβ oligomers in vitro (see ARF related news story). The U.S. Food and Drug Administration fast-tracked the compound for approval in April 2007.
The Phase 2 trial enrolled approximately 353 patients with mild to moderate AD, who were divided into three treatment arms and one placebo. Nine deaths have been recorded in patients treated with the two highest doses. The company release states that “A direct relationship between ELND005 and these deaths has not been established.” Nevertheless, the company and its partner, Transition Therapeutics, Inc., Toronto, Canada, made the decision to drop the two highest doses in consultation with the Independent Safety Monitoring Committee.
For more information, see the company press release.—Tom Fagan.